This invention relates to rapid throughput screening of combinatorial libraries. More particularly, the invention relates to methods and devices for reducing data acquisition time for spectroscopic analysis and imaging of multiple samples.
From the analytical perspective, quantification of a chemical property requires that the data can be analyzed with high confidence that any variation in the measured signal is due to a change of a chemical property of the sample, and not to variation in the measurement system. The quality of analysis of samples from combinatorial libraries is determined by a number of factors, the most important of which are the speed of measurement (screening throughput), reproducibility (precision), and accuracy. Precision generally will improve as the measured quantity due to the parameter of interest (signal) increases in comparison to the measured quantity due to general background (noise). For a variety of analytical techniques, increasing signal integration time improves signal quality. For high throughput screening of large numbers of samples, however, increasing integration time is often impractical.
Also, in many cases, the measured signal is proportional to sample size. For example, in Raman and fluorescence spectroscopy, the measured signal is directly proportional to the illuminated sample volume. Similarly, in absorption, mass-spectrometric, ionization, gravimetric, and other types of detection systems, the sample must be large enough to provide a detectable change in instrument response. However, developing new products and processes often requires combinatorial approaches that utilize multiple small-scale reactions arranged in an array format. Although efficient from the standpoint of cost, the small sample size is often accompanied by a decrease in signal, thus requiring long data acquisition times per sample.
Although many analytical techniques can be used to analyze libraries of small individual samples, these detection schemes are generally not practical because of the long sample integration times needed to analyze small samples. Thus, there is a need to develop a method by which signal integration time, and therefore overall data acquisition time, is reduced to a point where it no longer limits methods of analysis.
The present invention comprises methods and devices for reducing sample integration time using mathematical transform analysis and, thereby, significantly reducing the time required for screening multiple samples. The invention is particularly suited for screening combinatorial libraries comprising multiple samples of small volume.
In one aspect, the invention comprises a method for reducing the time required for analyzing at least one sample for a parameter of interest which comprises collecting analytical data from a sample using a predetermined integration time Ta and applying mathematical transform analysis on the data, wherein the mathematical transform analysis is performed using conditions designed to achieve a pre-determined signal quality response function value comprising the value obtained when samples are analyzed without mathematical transform analysis using integration time Tb, wherein Tb is greater than Ta.
In another aspect, the invention comprises an apparatus for analyzing at least one sample for a parameter of interest using a pre-determined signal quality response function which comprises: a collecting system for collecting analytical data comprising the parameter of interest from a sample; a processing system for processing the analytical data; a screening rate accelerator toolbox for applying mathematical transform analysis to the data; a data analysis system for determining whether the data processed by the screening rate accelerator toolbox satisfies a pre-determined signal quality response function value; and a statistical toolbox for analyzing the processed data for the parameter of interest.
The foregoing focuses on the more important features of the invention in order that the detailed description which follows may be better understood and in order that the present contribution to the art may be appreciated. There are additional features of the invention which will be described hereinafter and which will form the subject matter of the claims appended hereto. It is to be understood that the invention is not limited in its application to the details as set form in the following description and drawings, but is capable of other embodiments and of being practiced or carried out in various ways.